Edinburgh Research Explorer

Dr Will Cawthorn

Chancellor's Fellow

Profile photo

Willingness to take Ph.D. students: Yes

Education/Academic qualification

Doctor of Philosophy (PhD), University of Cambridge
The Molecular Mechanisms of Anti-Adipogenesis by Tumour Necrosis Factor-alpha
Bachelor of Arts, University of Cambridge
Natural Sciences (Biochemistry)
Master of Natural Science at Cambridge University, University of Cambridge
Biochemistry

My research in a nutshell

I study the formation and function of bone marrow adipose tissue (BMAT), a major component of our bone marrow that may have broad implications on health and disease.

One striking observation is that, unlike other types of adipose tissue, BMAT accumulates during conditions of starvation, including caloric restriction (CR) in animals and in human patients with anorexia nervosa. Therefore, a key focus of my lab is to determine the causes and consequences of BMAT accumulation during CR. To do so we use a combination of preclinical models, cutting-edge biomedical imaging, and clinical sample analyses. Our aim is to establish how BMAT impacts metabolic homeostasis, haematopoiesis, cardiovascular function and skeletal health.

There is currently much interest in using CR, or pharmacological CR mimetics, to prevent and treat chronic diseases. In pursuing our studies of CR and BMAT, my lab has identified striking sex differences, with females resisting many of the metabolic benefits of CR. This has implications for the use of CR and/or CR mimetics to improve health. Thus, my lab is now also investigating the mechanisms underlying these sex differences. Understanding these mechanisms might reveal new approaches for treating chronic diseases.

Finally, my lab is exploring population-level techniques to dissect the formation and function of BMAT in humans, both in normal physiology and disease.

More information can be found elsewhere on the Centre for Cardiovascular Science website, and via my profile on Edinburgh Research Explorer (which includes further details of my research, publications, funding and other activities).

Research Interests

White adipose tissue (WAT) is a key regulator of metabolic homeostasis, both as a site for energy storage and as an endocrine organ. The past generation has seen extensive research into WAT biology, fuelled largely by the public health burden posed by obesity and associated diseases. As such, WAT formation and function is now relatively well understood. Adipocytes also exist in bone marrow, yet in contrast to WAT, our understanding of such bone marrow adipose tissue (BMAT) is extremely limited. This ignorance is surprising: BMAT accounts for up to 70% of bone marrow volume in healthy adult humans, which suggests that BMAT has a role in normal human physiology. BMAT further increases in conditions of altered bone formation or metabolic health. For example, increased BMAT occurs in osteoporosis, suggesting that BMAT might contribute to the bone fragility that defines this disease. Perhaps most bizarrely, BMAT formation increases in starvation states, such as during caloric restriction (CR) in animals or in human patients with anorexia nervosa. This is in stark contrast to WAT, which is broken down during starvation to be used as fuel. CR has numerous health benefits, including increased lifespan, decreased risk of cancer and cardiovascular disease, and metabolic benefits such as enhanced fat breakdown and insulin sensitivity. BMAT also increases in response to treatment with anti-diabetic drugs such as thiazolidinediones or fibroblast growth factor-21, which, like CR, enhance insulin sensitivity. These clinical observations raise the possibility that BMAT directly promotes insulin sensitivity and metabolic health. However, whether BMAT impacts metabolic homeostasis remains unknown. Such knowledge could reveal new approaches to treat metabolic diseases. Thus, there is a critical need to understand the functions of BMAT.

 

My postdoctoral research revealed that, during CR, BMAT is a key source of adiponectin, a hormone that helps to maintain insulin sensitivity and fat breakdown, and which is linked to decreased risk of obesity-associated cancers, cardiovascular disease and diabetes. My postdoctoral work further revealed that BMAT expansion is required for skeletal muscle to adequately adapt to CR. This suggests that, as an endocrine organ, BMAT can exert systemic effects in metabolically relevant peripheral tissues.

My lab is now building on these observations by addressing the following questions (and their broader implications):

  1. What factors regulate BMAT formation in normal development, and aberrant BMAT expansion in disease states? Can we manipulate BMAT formation to achieve improved health outcomes?
  2. Does BMAT contribute to the impact of CR on metabolic homeostasis, cardiovascular risk, skeletal remodelling, haematopoiesis and/or immune function? What is the evolutionary function of BMAT, and how might this impact human health and disease?
  3. Does adiponectin contribute to the above effects of CR? What is the evolutionary function of adiponectin?
  4. We have found striking sex differences in the effects of CR on metabolic and immune function: What are the mechanisms underlying these sex differences? Can these be targeted to develop improved strategies to prevent and treat chronic disease?
  5. BMAT in humans can be measured non-invasively using magnetic resonance imaging (MRI) or spectroscopy (MRS). Can this be done at a population-level to reveal new insights into BMAT formation and function?

By pursuing the above questions, my research aims to reveal fundamental new knowledge about how BMAT, adiponectin and CR impact normal physiology and diverse disease states.

Current Research Interests

My current research addresses why BMAT expands during CR, and investigating if BMAT impacts metabolic health. Our previous publications in Cell Metabolism (PMID 24998914), Endocrinology (PMID 26696121) and Frontiers in Endocrinology (PMC5030308) provide some insights toward these questions. I am also interested in sex differences in the metabolic and other effects of CR, based on our findings in mice which show that females, unlike males, do not lose fat mass or improve glucose tolerance in response to CR. Notably, in collaboration with other groups, we have found similar differences in humans. Finally, we have shown that BMAT is a major source of increased circulating adiponectin during CR. Therefore, we are now investigating the function of this hormone during CR.

Improving our knowledge of BMAT formation and function might shed new light not only on normal human physiology, but also on diseases such as diabetes, osteoporosis, and cardiovascular disease. Similarly, by better understanding the mechanisms through which CR exerts diverse effects, we may be able to identify fundamental evolutionary pathways, as well as improved CR-related strategies to treat chronic diseases. Such knowledge will be vital if we are to reduce the public health impact of globally relevant health problems.

Websites

Research students

Current students:

  • Richard Sulston (BHF-funded PhD student)
  • Andrea Lovdel (CMVM-funded PhD student)
  • Domenico Mattiucci (visiting PhD student from Italy)
  • Benjamin Thomas (BHF-funded PhD student)

Previous students:

  • Iris Pruñonosa (visiting Erasmus student, now a student in CVS on the BHF 4-year PhD programme)
  • Alexandre Lafond, Diana Said, Matthew Sinton, Xuan Han, Holly Woodward (Previous MScR students)
  • Fiona Roberts, Rachel Bell (previous BSc Hons student)
  • Caitlin Jones, Catherine Redshaw and Richard West (previous summer undergraduate students)

Administrative Roles

  • Secretary and founding member of the International Bone Marrow Adiposity Society (BMAS; http://bma-society.org/).
  • Member of the Editorial Board for Diabetes
  • Member of the CVS Seminars and Symposium Committee.
  • Member of the CVS Social and Communications Committee.
  • Coordinator (with Prof Scott Webster) of the CVS Twitter account (@EdinUniCVS)
  • Coordinator (with Prof Nik Morton, Dr James Minchin and Dr Ruth Morgan) of the CVS Metabolism, Obesity and Diabetes (MOD) theme Twitter account (@EdinUniMetabol)
  • Coordinator of the BMAS Twitter account (@BMA_Society)

Teaching

Since moving to the University of Edinburgh in January 2015 I have supported students and postdoctoral trainees in the following ways:

  • Currently supervising one postdoctoral research fellow (Karla Suchacki), two four-year BHF-funded PhD students (Richard Sulston and Ben Thomas), one college-funded PhD student (Andrea Lovdel), and one visiting PhD student (Domenico Mattiucci). Co-supervisor for a second college-funded PhD student (Rebecca Wafer).
  • Lecturer for the MScR in Cardiovascular Science and undergraduate Endocrine Physiology and Pharmacology Honours course.
  • Previously supervised five Master's students (Alex Lafond, Diana Said, Matthew Sinton, Xuan Han, Holly Woodward), one ECAT researcher (Tyler Morrison), one visiting Erasmus student (Iris Pruñonosa) and five University of Edinburgh undergraduates during their Honours Projects or summer studentships in my lab.
  • Previously supervised one visiting postdoctoral researcher (Juilia Münzker) who has since obtained a permanent position in Germany.
  • Currently mentoring one postdoctoral researcher at the University of Edinburgh. Previously served as a mentor to two postdoctoral researchers who have since obtained a positions at other universities in the UK and USA.

Positions available

I am interested in hearing from enthusiastic candidates for PhD or Postdoctoral research projects. Please get in touch by email if you're interested.

Collaborative Activity

I am the Secretary and a founding member of the International Bone Marrow Adiposity Society (BMAS, http://www.bma-society.org/). This was established through my membership of an EU consortium called BoneAHEAD (Bone Adiposity in HEalth and Disease; http://www.boneahead.com/). The aim of BoneAHEAD is to apply for EU funding to advance our knowledge of BMAT, to train PhD students, to forge new collaborations within and beyond academia, and to translate understanding of BMAT to yield economic and public health benefits.

I am the lead PI on a collaborative MRC proposal that aims to establish methods for population-level imaging of BMAT. This includes co-Is from the Universities of Edinburgh, Dundee and Westminster, spanning diverse fields of imaging, genomics and adipose biology. 

My lab has forged other collaborations around the UK and internationally, based on our expertise in BMAT analysis.

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